Gadea A, López-Colomé A M
Instituto de Fisiología Celular, Departamento de Neurociencias, UNAM, México, D.F., México.
J Neurosci Res. 2001 Mar 15;63(6):461-8. doi: 10.1002/jnr.1040.
The termination of chemical neurotransmission in the central nervous system (CNS) involves the rapid removal of neurotransmitter from synapses. This is fulfilled by specific transport systems in neurons and glia, including those for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. Glial cells express the cloned Na(+)/Cl(-)-dependent, high-affinity GABA transporters (GATs) GAT1, GAT2, and GAT3, as well as the low-affinity transporter BGT1. In situ hybridization and immunocytochemistry have revealed that each transporter shows distinct regional distribution in the brain and the retina. The neuronal vs. glial localization of the different transporters is not clear-cut, and variations according to species, neighboring excitatory synapses, and developmental stage have been reported. The localization, stoichiometry, and regulation of glial GATs are outlined, and the participation of these structures in development, osmoregulation, and neuroprotection are discussed. A decrease in GABAergic neurotransmission has been implicated in the pathophysiology of several CNS disorders, particularly in epilepsy. Since drugs which selectively inhibit glial but not neuronal GABA uptake exert anticonvulsant activity, clearly the establishment of the molecular mechanisms controlling GATs in glial cells will be an aid in the chemical treatment of several CNS-related diseases.
中枢神经系统（CNS）中化学神经传递的终止涉及神经递质从突触的快速清除。这是通过神经元和神经胶质细胞中的特定转运系统实现的，包括那些负责γ-氨基丁酸（GABA，大脑中的主要抑制性神经递质）的转运系统。神经胶质细胞表达克隆的Na(+)/Cl(-)依赖性高亲和力GABA转运体（GATs）GAT1、GAT2和GAT3，以及低亲和力转运体BGT1。原位杂交和免疫细胞化学研究表明，每种转运体在大脑和视网膜中都呈现出独特的区域分布。不同转运体在神经元和神经胶质细胞中的定位并不明确，并且已有报道称其存在物种、相邻兴奋性突触和发育阶段的差异。本文概述了神经胶质细胞GATs的定位、化学计量和调节，并讨论了这些结构在发育、渗透调节和神经保护中的作用。GABA能神经传递的减少与几种中枢神经系统疾病的病理生理学有关，尤其是癫痫。由于选择性抑制神经胶质细胞而非神经元GABA摄取的药物具有抗惊厥活性，因此明确控制神经胶质细胞中GATs的分子机制将有助于对几种中枢神经系统相关疾病进行化学治疗。
